Viral infection is a major cause of disease and death throughout the world. To study and understand viruses and their diseases it is desirable to develop devices and methods for virus detection, characterization of viral growth and propagation, and quality control for nanoparticle production and other medical uses.
Viral disease can propagate in a cell or organism rapidly, and can be transmitted quickly and easily in many cases. Therefore, it is important to be able to rapidly measure and characterize the mass of a virus, a single whole virus, and virus particles.
Some methods for viral analysis include using a nanoscale cantilever beam operating as a mass detector, using a quartz crystal microbalance (QCM), using charge reduced electrospray size spectrometry, measuring discrete conductance changes characteristic of binding and unbinding, and microscopy-based mass spectrometry. Drawbacks of all of these methods include requiring a complex sample operation that is inconvenient for infectious materials. Thus, these methods have not achieved rapid and convenient detection at a single virus level.
It would be very useful to be able to detect and characterize viruses and virus particles by mass spectrometry. For example, it is desirable to measure and characterize viruses such as human immunodeficiency virus (HIV), flu viruses, and SARS virus, among many others.
Currently, mass spectrometers are limited to detecting analytes with m/z much lower than 108. Commercial mass spectrometers typically use a charge amplification device such as a channeltron, electromultiplier or microchannel plate (MCT) for detection. A charge amplification device does work well with the m/z of the charged particle higher than about 105 to 106.
It has been shown that detecting both m/z and z of a single microparticle can be done at the same time using a mass spectrometer which can measure charge directly. The mass of a microparticle or cell could be obtained. In general, when z and m/z can be correctly obtained, the mass (m) can be revealed. The mass of a microparticle or cell could be obtained.
The mass distribution of cells or microparticles could be determined by measuring mass-to-charge ratios (m/z) and charge (z) simultaneously.
One drawback to this approach is that the number of charges on each particle needs to be high, because electronic charge measurement devices have an electronic background noise of about 50 to 500 electrons. When the number of charges on the particle to be measured is less than about 500, it is difficult to obtain the correct mass.
Most cells or microparticles in a vacuum have more than 1000 charges.
Another drawback to this approach is that to obtain the correct z, only one cell or one particle can be measured by the detector at any one time.
Because of these drawbacks, this approach cannot be applied to the measurement of a nanoparticle or virus. For example, a nanoparticle or a virion typically has less than 500 charges so that the mass cannot be determined accurately due to the electronic background.
It is also difficult to quickly measure the masses of nanoparticles. One approach is to use electron microscopy to measure the size of a nanoparticle and calculate the mass based on the density. However, this is a tedious and very time-consuming approach.
There is a continuing need for apparatus and methods for rapidly measuring the masses of nanoparticles, detecting a virus, a nanoparticle, a single whole virus, a virion, or a virus particle using mass spectrometry.